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Trial record 6 of 48 for:    necrotizing enterocolitis | NIH

Metronidazole Pharmacokinetics (PK) in Premature Infants (PTN_METRO)

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ClinicalTrials.gov Identifier: NCT01222585
Recruitment Status : Completed
First Posted : October 18, 2010
Results First Posted : December 18, 2013
Last Update Posted : February 6, 2014
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Information provided by (Responsible Party):
Michael Cohen-Wolkowiez, Duke University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Serious Systemic Infections
Necrotizing Enterocolitis
Intervention Drug: Metronidazole
Enrollment 24

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Metronidazole IV
Hide Arm/Group Description Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Period Title: Overall Study
Started 24
Completed 24
Not Completed 0
Arm/Group Title Treatment
Hide Arm/Group Description Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Days
Number Analyzed 24 participants
27
(1 to 82)
[1]
Measure Description: Post Natal Age (Days)
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Weeks
Number Analyzed 24 participants
25
(23 to 31)
[1]
Measure Description: Gestational age (weeks)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
16
  66.7%
Male
8
  33.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Hispanic or Latino
6
  25.0%
Not Hispanic or Latino
18
  75.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
1
   4.2%
Black or African American
7
  29.2%
White
16
  66.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
Birth Weight  
Median (Full Range)
Unit of measure:  Grams
Number Analyzed 24 participants
740
(431 to 1466)
1.Primary Outcome
Title Area Under the Curve at Steady State
Hide Description Area under the curve at steady state (AUCss)
Time Frame pre-dose: 30 min; post-dose:10 min, 3-4,6-8, 12-13, 24-25, 36-37, 48-49, 72-73 hours post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate this PK parameter.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: mg*hr/L
178.0
(66.0 to 472.0)
2.Primary Outcome
Title Loading Dose Maximum Concentration
Hide Description Loading Dose Maximum concentration (Cmax)
Time Frame 2-5 days of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The sample size contains the number of subjects that had the sample of interest collected.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 19
Median (Full Range)
Unit of Measure: mg/L
16.54
(9.18 to 19.63)
3.Primary Outcome
Title Loading Dose Minimum Concentration
Hide Description Loading Dose Minimum Concentration (mg/L)
Time Frame 2-5 days of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The sample size contains the number of subjects that had the sample of interest collected.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 17
Median (Full Range)
Unit of Measure: mg/L
9.20
(3.21 to 12.82)
4.Primary Outcome
Title Multiple Dose Maximum Concentration
Hide Description Multiple Dose Maximum Concentration (mg/L)
Time Frame 2-5 days of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the multiple dose PK parameter.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: mg/L
16.51
(8.71 to 34.05)
5.Primary Outcome
Title Multiple Dose Minimum Concentration
Hide Description Multiple Dose Minimum Concentration (mg/L)
Time Frame 2-5 days of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The sample size contains the number of subjects that had the sample of interest collected.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 21
Median (Full Range)
Unit of Measure: mg/L
11.62
(1.29 to 27.05)
6.Primary Outcome
Title Clearance
Hide Description Clearance (L/h/kg)
Time Frame 2-5 days of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the PK parameter.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: L/h/kg
0.043
(0.016 to 0.105)
7.Primary Outcome
Title Volume of Distribution
Hide Description Volume of Distribution (L/kg)
Time Frame 2-5 days of study drug administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the PK parameter.
Arm/Group Title Metronidazole IV
Hide Arm/Group Description:
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Overall Number of Participants Analyzed 20
Median (Full Range)
Unit of Measure: L/kg
0.99
(0.38 to 2.67)
Time Frame From first dose through 10 days post dose.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment
Hide Arm/Group Description Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
All-Cause Mortality
Treatment
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment
Affected / at Risk (%)
Total   5/24 (20.83%) 
Cardiac disorders   
Cardiac arrest  1 [1]  1/24 (4.17%) 
Gastrointestinal disorders   
Necrotising colitis  1 [1]  2/24 (8.33%) 
General disorders   
Death  1 [1]  1/24 (4.17%) 
Infections and infestations   
Septic shock  1 [1]  1/24 (4.17%) 
Renal and urinary disorders   
Renal failure acute  1 [1]  1/24 (4.17%) 
Surgical and medical procedures   
Patent ductus arteriosus repair  1 [1]  1/24 (4.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra
[1]
Not related to study drug
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment
Affected / at Risk (%)
Total   17/24 (70.83%) 
Endocrine disorders   
Endocrine disorders Adrenal Insufficiency  1 [1]  4/24 (16.67%) 
General disorders   
Other non-serious, infrequent adverse events  1 [1]  7/24 (29.17%) 
Nervous system disorders   
Convulsion  1 [1]  3/24 (12.50%) 
Skin and subcutaneous tissue disorders   
Dermatitis diaper  1 [1]  3/24 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra
[1]
Not related to study drug
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Michael Cohen-Wolkowiez, MD
Organization: Duke Clinical Research Institute
Phone: 919668-8812
Responsible Party: Michael Cohen-Wolkowiez, Duke University
ClinicalTrials.gov Identifier: NCT01222585     History of Changes
Other Study ID Numbers: Pro00024571
HHSN27500003I ( Other Grant/Funding Number: NICHD )
First Submitted: October 6, 2010
First Posted: October 18, 2010
Results First Submitted: July 23, 2013
Results First Posted: December 18, 2013
Last Update Posted: February 6, 2014